An Aurora kinase inhibitor AMG900 inhibits glioblastoma cell proliferation by disrupting mitotic progression

摘要

The Aurora kinase family of serine/threonine protein kinases comprises Aurora A, B, and C and plays an important role in mitotic progression. Several inhibitors of Aurora kinase have been developed as anti‐cancer therapeutics. Here, we examined the effects of a pan‐Aurora kinase inhibitor, AMG900, against glioblastoma cells. AMG900 inhibited proliferation of A172, U‐87MG, and U‐118MG glioblastoma cells by upregulating p53 and p21 and subsequently inducing cell cycle arrest and senescence. Abnormal cell cycle progression was triggered by dysregulated mitosis. Mitosis was prolonged due to a defect in mitotic spindle assembly. Despite the presence of an unattached kinetochore, BubR1, a component of the spindle assembly checkpoint, was not recruited. In addition, Aurora B was not recruited to central spindle at anaphase. Abnormal mitotic progression resulted in accumulation of multinuclei and micronuclei, a type of chromosome missegregation, and ultimately inhibited cell survival. Therefore, the data suggest that AMG900‐mediated inhibition of Aurora kinase is a potential anti‐cancer therapy for glioblastoma.